3-(Imidazol-1-ylalkyl)indoles as selective inhibitors of thromboxane synthetase,pharmaceutical compositions thereof, and methods for preparing them.

摘要

Substituted 3-(imidazol-1-ylmethyl)indoles of the formula:
<CHEM>
wherein R<1> is hydrogen or lower alkyl;
R<2> is hydrogen, lower alkyl, lower cycloalkyl, adamantyl, or a phenyl or benzyl group in which the benzene ring is optionally mono-substituted with halogen, hydroxy, lower alkyl, lower alkoxy or trifluoromethyl;
R<3> is hydrogen, lower alkyl, allyl, 3-methyl-allyl, lower cycloalkyl-methyl, lower cycloalkyl-ethyl, lower alkoxy- lower alkyl, di(lower alkyl)amino-lower alkyl, lower alkanoyl, lower cycloalkyl-carbonyl, or a benzyl or benzoyl group in which the benzene ring is optionally substituted as in R<2>;
and R<4> is hydrogen, lower alkyl, lower alkoxy, halogen, hydroxy, trifluoromethyl, di(lower alkyl)amino, or a benzyloxy group in which the benzene ring is optionally substituted as in R<2>;
are described which are selective inhibitors of the action of the thromboxane synthetase enzyme, but which do not significantly affect the actions of the prostacyclin synthetase or cyclo-oxygenase enzymes, and which are therefore useful in the treatment of ischaemic heart disease, stroke, transient ischaemic attack and migraine. All the compounds, except that in which R<1>, R<2>, R<3> and R<4> are each hydrogen, are novel. Methods for their preparation are also described.